The promise of new antiepileptic drugs

Abstract

Epilepsy is the most common serious disorder of the brain and comprises a wide range of different conditions with varying aetiologies. The long-established antiepileptic drugs (AEDs) control seizures in 50% of patients developing partial seizures, and 60-70% of those developing generalized seizures. Several AEDs were made available in the 1990s. These drugs have efficacy, but have had only a modest impact on those with refractory epilepsies. A 50% seizure reduction, which is commonly used as an endpoint in clinical trials, confers little benefit to a patient. Of the newer AEDs, lamotrigine and oxcarbazepine are now licensed for use as monotherapy and vigabatrin has a monotherapy licence for infantile spasms. Careful and prolonged postmarketing surveillance is essential to detect adverse effects, which may not be evident in premarketing clinical trials. At this time, there are 10 AEDs currently in varying stages of clinical development. Current strategies for selecting an AED for a particular patient are crude. Magnetic resonance spectroscopic measures of cerebral neuro-transmitters and genetic analysis may allow better prediction of which drug is most likely to be efficacious and to have low risk of adverse effects. Present AEDs suppress the occurrence of seizures. Agents that prevent the development of epilepsy and which protect the brain from the consequences of seizures would be of great value, but it will be difficult to prove their effectiveness. At present AEDs are given continually and systemically. Local drug delivery is feasible and could avoid the adverse effects of AEDs. The combination of local drug delivery with prediction of seizure occurrence could revolutionize the treatment of currently refractory epilepsies.